The Effects Of Shenqi Fuzheng Injection On Oxidative Damage And Apoptosis In Mice With Viral Myocarditis

ObjectiveTo investigate the effects of Shenqi Fuzheng injection on the SOD,MDA and Fas/FasL with viral myocarditis induced by Coxsackie virus B3, and to explore its mechanism.MethodsUtilizing the cardiac tendency of Coxsackie virus B3 to make the model of viral myocarditis in mice by injecting Coxsackie virus B3 to the peritoneal cavity of the mice.120 Balb/c male mice were divided into 5 groups at random:blank group,virus model group, ribavirin group,low dose Shenqi Fuzheng injection(be short for ShenQi) group and high dose ShenqiFuzheng injection group and they were injected with the ShenqiFuzheng injection for 30 days,then observed with the change of their mental state,activity and their diet. By collecting their specimen and blood in the third day,the 10th day and the 30th day,SOD content in serum was determined by xanthine oxidase. MDA content in serum was determined by Thibabituric Acid TBA. Pathological changes of cardiac muscle were observed by HE dyeing. Electron microscope and TUNEL were used to detect apoptotic cells. Immunohistochemistry method was used to examine the expression of Fas and FasL. Semiquantitative analysis of Fas and FasL mRNA in myocardial was used by RT-PCR method.Results1. Compared with the blank group: infection symptom,losing weight,mortality were the most serious during the 4th to 10th days of model group(P<0.01).Compared with the model group,all treatment groups could amendment the symtom and decrease the mortality to some degree. ShenQi high dose group had the most obvious effect.2. Compared with the blank group: myocardial histopathologic scores of model group increased in the 3th,10th,30th days(P<0.01). It had the most obvious effect in the 10th day.Foliated cadiocyte apomorphosised and necrosised, the endochylema was nonuniform staining,cytolemma was damaged,nucleus atrophiaed,dyed darker, lots of inflammatory cells infiltration,visable some interstitial edema. In the 30th day, inflammatory cells infiltration reduced,fibrocyte hyperplasied. Myocardial ultrastructure was observed by electron microscope.It was significant that myocardial damaged at 3 points,the most serious in the 10th day. Myofibrils were extremely disorder and sparseness,intercalated disk structure was not clear, mitochondria were swelling, the chromatin density of nucleus was increased and seted edge with apoptosis. In the 30th day, parts of mitochondria were swelling and nucleuses were apoptosised. Focal collagen fibers increased. The content of SOD decreased in the 3th day.It obviously decreased in the 10th day and increased gradually in the 30th day. The content of SOD and apoptosis index (AI), the level of Fas/FasL protein and the mRNA expression increased at 3 points(P<0.01).It reached the peak in the 10th day,and decreased in the 30th day.3. In the 3th,10th,30th days, the content of SOD in the model group showed significantly negative correlation with the changes of myocardial histopathologic scores (r=-0.702, P<0.01);The content of MDA,AI,the level of Fas/FasL protein and the mRNA expression showed significantly positive correlation with the changes of myocardial histopathologic scores(r=0.802,0.900,0.865,0.907,0.898,0.831,P<0.01);the level of Fas/FasL protein and the mRNA expression showed significantly positive correlation with the changes of AI(r=0.967,0.991,0.995,0.971,P<0.01);AI,the level of Fas/FasL protein and the mRNA expression showed significantly negative correlation with the changes of the content of SOD(r=-0.648,-0.752,-0.653, -0.673,-0.654,P<0.01);AI,the level of Fas/FasL protein and the mRNA expression showed significantly positive correlation with the changes of the content of MDA(r=0.720,0.814,0.738,0.755, 0.737, P<0.01).4. Compared with the model group, in the 3th day, myocardial histopathologic scores of all treatment group were reduced and myocardial ultrastructure damages were amendment, but there were not satistically significant among the three group(P>0.05).Both ShenQi high dose group and ribavirin group, the content of SOD was improved, the content of MDA was reduced(P < 0.05)and there was not satistically significant of ShenQi low dose group(P > 0.05);AI, the level of Fas/FasL protein and the mRNA expression of all treatment groups were not satistically significant to the model group(P>0.05).In the 10th day, myocardial histopathologic scores were reduced,myocardial ultrastructure damages were amendmented,the content of SOD was increased,the content of MDA,AI,the level of Fas/FasL protein and the mRNA expression were decreased in all treatment groups(P<0.05,P<0.01), ShengQi high dose group was the most obvious.It was satistically significant compared with the ribavirin group(P<0.01).In the 30th day,there were satistically significant in impoving each index of ShengQi high dose group and ShengQi low dose group(P<0.01,P<0.05).ShengQi low dose group was statistically significant compared with the ribavirin group(P<0.05)and not statistically significant compared with the ShengQi high dose group(P>0.05).Conclusion1.It can successfully make the model of viral myocarditis in mice by BALB/c mice after CVB3 infection.2.Withing the viral myocarditis, oxidative damage and apoptosis are exsistence and show significantly positive correlation.3.Shenqi Fuzheng injection can reduce myocardial pathological damage of viral myocarditis.4.Shenqi Fuzheng injection can reduce oxidative damage of viral myocarditis by increasing SOD content and decreasing MDA content.5.Shenqi Fuzheng injection can restrain apoptosis of viral myocarditis by decreasing the expression of Fas and FasL level.